Studies On Synthetic Methods Of Polysubstituted Furans, Cyclohexenones And Phenols From Acyclic Compounds

Since Kelber first synthesized theα?benzoyl ketene-(S,S)-acetal in 1910,α-oxo ketene-(S,S)-acetals chemistry has become an important division in organic chemistry through the development of near one hundred years.α-oxo ketene-(S,S)-acetals have proven to be especially important in the construction of a diverse array of polysubstituted carbo- and heterocyclic compounds. Facile and synthetic methods of polysubstituted furans cyclohexenones and phenols are attempted based onα-oxo ketene-(S,S)-acetals. Based on the research achievements of our group inα-oxo ketene-(S,S)-acetal chemistry in the past several years, my thesis under synthetic design, taking the synthesis ofα-oxo ketene-(S,S)-acetals andα-alkenoyl ketene (S,S)-acetals as foundation, explores a series of basic reactions whichα-oxo ketene-(S,S)-acetals andα-alkenoyl ketene (S,S)-acetals can react, and based on these basic reactions, we also carried out on the new synthetic methodologies for oxygen -containing heterocycle and carbocycles. The contents in this thesis mainly include four aspects:1. A set of functionalized allylic sulfides have been synthesized by a thiomethylation reaction based onα-oxo ketene-S, S-acetals 1. This three-component reaction, involving anα-oxo ketene-S,S-acetal 1, formaldehyde, and a thiol 2, is the first example of the Mannich-type thiomethylation of activated alkenes. Allylic sulfoxides are readily obtained by a highly regioselective oxidation of the corresponding allylic sulfides with use of m-CPBA as oxidant.2. We explored the applications of sulfoxides 4 in the construction of polyfunctionalized furans. As a result, a [3 + 2] annulation reaction of allylic sulfoxides 4 and aldehydes 5 was uncovered. The key features of this furan synthesis are that the combination of the properties of sulfoxide (the alkylsulfinyl group is either an activating group of the adjacent methylene or a good leaving group) and ketene-S,S-acetal (substitution reaction of alkylthio group) contributes to the formation of furan scaffold and that the resulting furan derivatives, bearing a wide range of functional groups such as alkylthio, alkylamino, or carbonyl, etc., can be taken as valuable synthons for the preparation of various synthetically useful compounds. It is also of great interest to note that the presented [3 + 2] annulation gives furans in good to high yields from readily available starting materials under mild conditions.3. An efficient and regiospecific [5C + 1C] annulation reaction ofα-alkenoyl ketene (S,S)-acetals with aryl methyl ketones, the less active methylene compounds, was disclosed, and thus highly substituted 2-cyclohexanones were synthesized in high yields with high stereoselectivities. On the basis of this synthetic strategy, a facile route to sterically hindered benzophenones was developed via the iodonation-aromatization of 2-cyclohexenones obtained above with I2 in MeONa/MeOH basic medium. Furthermore,the direct preparation of benzophenones fromα-alkenoyl ketene (S,S)-acetals and aryl methyl ketones following a sequential [5 + 1] annulation-iodonationaromatization procedure in a one-pot operation was achieved as well.4. A facile and efficient one-pot synthesis of polyfuctionalized phenols from ketene (S,S)-acetals, aldhydes and methyl ketone has been developed. Furthermore, one-pot four component direct synthesis of polyfuctionalized phenols from 1, 3-dicarbonyl compounds was successful developed as well.